Protein stabilization formulations

Abstract

The present invention is directed to stabilizing Bone Morphogenetic Protein in various lyophilized formulations and compositions. The present invention comprises formulations primarily including trehalose as an excipient for lyophilized compositions and their subsequent storage and reconstitution, and can also optionally include other excipients, including buffers and surfactants.

1. A composition comprising rhGDF-5, glycine, and an amount of trehalose sufficient to stabilize said rhGDF-5, wherein said composition has a pH of about 2.5 to about 3.5. 
     
     
       2. A device for implanting in a mammal, said device comprising a biocompatible matrix and a composition comprising rhGDF-5, glycine, and an amount of trehalose sufficient to stabilize said rhGDF-5, wherein said composition has a pH of about 2.5 to about 3.5. 
     
     
       3. The device of  claim 2 , wherein said biocompatible matrix is selected from the group consisting of collagen, mineralized collagen, salts of calcium phosphate, ceramics containing calcium, autogenic bone, allogenic bone, xenogenic bone, polylactide (PLA), polyglycolide (PGA), PLA-PGA co-polymers, polycarbonate, polycaprolactone, and mixtures thereof. 
     
     
       4. A surgical kit comprising a biocompatible matrix and a lyophilized BMP composition, wherein said lyophilized BMP composition comprises rhGDF-5, glycine and an amount of trehalose sufficient to stabilize said rhGDF-5, wherein said composition has a pH of about 2.5 to about 3.5. 
     
     
       5. The composition of  claim 1 , wherein said composition is lyophilized. 
     
     
       6. A method of stabilizing a rhGDF-5 comprising the steps of:
 providing a composition containing rhGDF-5, glycine, and an amount of trehalose sufficient to stabilize said rhGDF-5, wherein said composition has a pH of about 2.5 to about 3.5, and 
 lyophilizing the composition. 
 
     
     
       7. A method of treating a patient having a defect selected from the group consisting of a bone defect, a cartilage defect, a tendon defect, a ligament defect, and an intervertebral disc defect, said method comprising the steps of:
 providing a composition to said patient, wherein said composition comprises a biocompatible matrix, rhGDF-5, glycine, and an amount of trehalose sufficient to stabilize said rhGDF-5, wherein said composition has a pH of about 2.5 to about 3.5; and 
 implanting said composition into said defect.